School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, China.
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin, China.
Pest Manag Sci. 2021 Oct;77(10):4691-4700. doi: 10.1002/ps.6510. Epub 2021 Jun 26.
Plant diseases have been gripping agricultural production, seriously affecting the growth and yields of crops. Marine natural products are an important source for novel drugs discovery. In this work, pityriacitrin marine alkaloids were selected as the parent structures. A series of pityriacitrin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities.
Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 3a, 3e, 8f, 8g, and 9g displayed higher anti-TMV activities than ningnanmycin at 500 μg·mL . Mechanism research revealed that 3a could bind to TMV CP with an excellent affinity (K = 8.67 × 10 L·mol ), thus interfere with the assembly of virus particles. These alkaloids also showed broad-spectrum fungicidal activities against eight kinds of phytopathogenic fungi. Compound 5f with 1.43-3.84 μg·mL EC value against three fungi emerged as a new fungicidal candidate.
Pityriacitrin alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 3a and 5f with excellent activities emerged as new candidates for antiviral research and fungicidal research, respectively. Current work provided a new idea for the molecular design and development of novel plant virus and fungi inhibitors in the future. © 2021 Society of Chemical Industry.
植物病害一直困扰着农业生产，严重影响了作物的生长和产量。海洋天然产物是新型药物发现的重要来源。在这项工作中，选择扁蒴藤海洋生物碱作为母体结构。本文从结构优化的角度出发，设计、合成了一系列扁蒴藤生物碱类似物，并对其抗病毒活性和抑菌活性进行了评价。
大多数化合物的抗病毒活性均优于利巴韦林。特别是化合物 3a、3e、8f、8g 和 9g 在 500μg·mL 时表现出比宁南霉素更高的抗 TMV 活性。机制研究表明，3a 与 TMV CP 具有极好的亲和力（K = 8.67×10 L·mol ），从而干扰病毒粒子的组装。这些生物碱还表现出对 8 种植物病原菌的广谱抑菌活性。化合物 5f 对 3 种真菌的 EC 值为 1.43-3.84μg·mL ，是一种新的抑菌候选药物。
首次合成和评价了扁蒴藤生物碱及其衍生物的抗 TMV 和抑菌活性。化合物 3a 和 5f 表现出优异的活性，分别成为抗病毒和抑菌研究的新候选药物。本研究为未来新型植物病毒和真菌抑制剂的分子设计和开发提供了新的思路。 © 2021 英国化学学会。
